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Background Recent studies have suggested a blunted immune response to messenger RNA vaccines in solid organ transplant (SOT) recipients. Given the paucity of data on adenovirus vector vaccines use in immunosuppressed SOT recipients, we sought to describe the safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine in a heart transplant population. Methods Heart transplant recipients aged 18 to 70 years scheduled to receive 2 doses of the ChAdOx1 nCoV-19 vaccine were enrolled into a prospective study involving serum analysis to define their antibody response. An antibody concentration against the spike protein receptor-binding domain of ≥0.8 U/mL was deemed a detectable antibody response. Results A total of 99 heart transplant recipients (mean age 51 ± 12.5 years, 28% female) were enrolled. No major adverse events were recorded after vaccination; minor symptoms included injection site pain (24%), fatigue (21%) and headache (14%). Of 7 patients with prior SARS-CoV-2 confirmed by PCR testing, all (100%) had detectable antibody responses following first and second vaccine doses. In those with no prior SARS-CoV-2 infection (n = 92), 24% (n = 22) showed an antibody response after dose 1, increasing to 34.8% (n = 32) after dose 2, p < 0.001. Chronic kidney disease (CKD) stage ≥3 (OR 4.7, 95% CI 1.5-15, p = 0.009) and mycophenolate use (OR 4.1, 95% CI 1.2-14, p = 0.02) were independently associated with a nondetectable antibody response. Conclusions Almost two-thirds of heart transplant recipients aged 18 to 70 years without a history of prior SARS-CoV-2 infection failed to develop a detectable antibody response following administration of the ChAdOx1 nCoV-19 vaccine. Patient phenotyping may help predict which patients are less likely to develop detectable antibody responses.

The prevalence of sarcoidosis-related cardiomyopathy is increasing. Sarcoidosis impacts cardiac function through granulomatous infiltration of the heart, resulting in conduction disease, arrhythmia and/or heart failure. Diagnosis of cardiac sarcoidosis can be challenging and requires clinician awareness as well as differentiation from overlapping diagnostic phenotypes such as other forms of myocarditis and arrhythmogenic cardiomyopathy. Clinical manifestations, extracardiac involvement, histopathology, and advanced cardiac imaging can all lend support to a diagnosis of cardiac sarcoidosis. Mainstay therapy for cardiac sarcoidosis is immunosuppression, however no prospective clinical trials exist to guide management. Patients may progress to developing advanced heart failure or ventricular arrhythmia, for which ventricular assist device therapies or heart transplantation may be considered. The existing knowledge gaps in cardiac sarcoidosis call for an interdisciplinary approach to both patient care and future investigation to improve mechanistic understanding and therapeutic strategies.

Solid organ transplant recipients have demonstrated a blunted immune response to standard 2-dose vaccination against SARS-CoV-2. This study sought to determine the humoral response to heterologous booster vaccination (viral vector vaccine dose 1 and 2 + mRNA booster). Heart transplant recipients, aged 18 to 70 years of age who initially received two doses of the viral vector ChAdOx1 nCoV-19 vaccine followed by a BNT162b2 mRNA booster were recruited. A detectable antibody response in the absence of prior SARS-CoV-2 was the primary outcome measured. This was defined as an anti-spike titre of ≥0.8 U/mL on the Elecsys anti-SARS-CoV-2 S immunoassay. A total of 80 heart transplant patients (mean age 49 ± 13 years, 28% female) were included. Blood samples were drawn at a median of 30 (IQR 28-33) days after the BNT162b2 mRNA booster. The frequency of a detectable antibody response increased from 37.5% (n = 30) after dose 2 to 56% (n = 45) post dose 3 (p0.001). A non-detectable antibody response was significantly more common in recipients with a shorter time interval from transplantation (p0.001), lower likelihood of cardiac allograft vasculopathy (p = 0.003) and in those prescribed a triple versus dual immunosuppressant regime (p = 0.009) and a tacrolimus versus cyclosporine basedregimen (p = 0.007). Despite heterologous prime-booster vaccination 44% of this vulnerable population ultimately continue to have no detectable antibodies.

Background The diagnosis of cardiac sarcoidosis (CS) is challenging. Because of the current limitations of endomyocardial biopsy as a reference standard, physicians rely on advanced cardiac imaging, multidisciplinary evaluation, and diagnostic criteria to diagnose CS. Aims To compare the 3 main available diagnostic criteria in patients clinically judged to have CS. Methods We prospectively included patients clinically judged to have CS by a multidisciplinary sarcoidosis team from November 2016 to October 2017. We included only incident cases (diagnosis of CS within 1 year of inclusion). We applied retrospectively the following diagnostic criteria: the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG), the Heart Rhythm Society (HRS), and the Japanese Circulation Society (JCS) 2016 criteria. Results We identified 69 patients. Diagnostic criteria classified patients as follows: WASOG as highly probable (1.4%), probable (52.2%), possible (0%), some criteria (40.6%), and no criteria (5.8%); HRS as histological diagnosis (1.4%), probable (52.2%), some criteria (40.6%), and no criteria (5.8%); JCS as histological diagnosis (1.4%), clinical diagnosis (58%), some criteria (39.1%), and no criteria (1.4%). Concordance was high between WASOG and HRS (κ = 1) but low between JCS and the others (κ = 0.326). Conclusions A high proportion of patients clinically judged to have CS are unable to be classified according to the 3 main diagnostic criteria. There is low concordance between JCS criteria and the other 2 criteria (WASOG and HRS).

The association between atrial fibrillation (AF) and thromboembolic (TE) complications in left ventricular assist device (LVAD) recipients is controversial, and there is paucity of large-scale data evaluating the impact of AF on early outcomes after device implantation. Using the National Inpatient Sample, we identified hospitalizations where patients underwent LVAD implantation from 2010 to 2015. Multivariate logistic regression was used to evaluate the association of AF on in-hospital outcomes. A total of 18,378 patients (41.7% with AF) underwent LVAD implantation. Patients with AF were older (59.9 vs. 54.0 years, p

Cardiac sarcoidosis (CS) is frequently difficult to treat. Infliximab (IFX) is useful for extracardiac sarcoidosis, but its use in CS has been limited due to concerns about cardiotoxicity and an FDA blackbox warning about use in heart failure. We reviewed 36 consecutive patients treated with infliximab for CS refractory to standard therapies. IFX was initiated for patients with refractory dysrhythmias, moderate to severe cardiomyopathy, and evidence of persistent F-18 fluorodeoxyglucose uptake on positron emission tomography scan, despite standard therapies. We compared the prednisone dose, ejection fraction (EF), and dysrhythmias before and after IFX therapy. The prednisone-equivalent steroid dose decreased from a median of 20 mg at initiation of infliximab to 7.5 at 6 months and 5 mg at 12 months postinitiation of infliximab (p0.001). In the 25 patients with serial EF measurements, no statistically significant difference was detected in EF (41% at baseline, 42% at 6 months). Of the 16 patients with serial dysrhythmia data, there was a trend toward reduction of percent of patients with ventricular tachycardia (VT), from 32% at baseline, to 22% at 6 months and 19% at 12 months (p = 0.07). Adverse events were common, occurring in 6 of 36 patients, with 3 of 36 patients stopping infliximab for a prolonged period. In responder analysis, 24 patients improved in at least 1 of 3 outcome categories. In conclusion, infliximab may be useful for refractory cardiac sarcoidosis.

Increasing awareness of cardiac manifestations of sarcoidosis and the widespread availability of advanced imaging tests have led to a tidal wave of interest in a condition that was once considered rare. In this Focused Review, we explore important clinical questions that may confront specialists faced with possible cardiac involvement. In the absence of an ideal reference standard, three main sets of clinical criteria exist: the Japanese Ministry of Health and Welfare, the Heart Rhythm Society, and the World Association for Sarcoidosis and Other Granulomatous Disorders criteria. Once cardiac sarcoidosis is suspected, clinicians should be familiar with the prevalence of the disease in different clinical scenarios. Before obtaining advanced cardiac imaging, electrocardiogram, ambulatory electrocardiogram, echocardiogram, and B-type natriuretic peptide may be useful. The available therapies for cardiac sarcoidosis include immunosuppression, antiarrhythmic medications, heart failure medications, device therapy, ablation therapy, and heart transplantation. Contemporary data suggest that long-term survival in cardiac sarcoidosis is better than previously believed. There is no randomized controlled trial demonstrating benefits of screening, but screening is recommended based on observational data.

Malnutrition, sarcopenia, and cachexia are areas of increasing interest in the management of patients with heart failure (HF). This review aims to examine the serological markers useful in guiding the physician in identification of these patients. Traditional nutritional biomarkers including albumin/prealbumin, iron, and vitamin D deficiencies predict poor prognosis in malnutrition and HF. Novel biomarkers including ghrelin, myostatin, C-terminal agrin fragment, and adiponectin have been identified as possible substrates and/or therapeutic targets in cardiac patients with sarcopenia and cachexia, though clinical trial data is limited to date. Increased focus on nutritional deficiency syndromes in heart failure has led to the use of established markers of malnutrition as well as the identification of novel biomarkers in the management of these patients, though to date, their usage has been confined to the academic domain and further research is required to establish their role in the clinical setting.

Background Patient limitations guide selection of heart failure therapies, for which indications often specify New York Heart Association Class. Objectives To determine the extent of patient‐reported limitations during daily activities and compare to New York Heart Association class assigned by providers during the same visit, and to left ventricular ejection fraction (LVEF) group. Methods and Results While waiting for their appointment, 948 patients on return visits to an ambulatory HF clinic completed a written questionnaire assessing specific activity limitations, which were compared to physician‐assigned NYHA class during the same visit. Patient‐reported limitation to perform daily activity ranged from 25% for bathing to 61% for yardwork or housework and 71% for jogging or hurrying. Most patients who did not report limitations to perform daily life activities were correctly classified as NYHA I by the physicians (76%), but 12% of the 376 patients classified as NYHA I reported limitations to showering or bathing and 73% reported limitations while doing yardwork or house work. Limitation to walking was reported by 172 patients (50%) classified as class II. Limitations to walking one block were most common in patients with LVEF ≥40% compared to patients with LVEF

Cardiac resynchronization therapy (CRT) has been shown to be beneficial in patients with medically refractory heart failure. Although it has been found to be effective in a wide range of etiologies for nonischemic cardiomyopathy, its role in improving remodeling and survival of patients with cardiac sarcoidosis (CS) remains undefined. We performed a retrospective review of all patients at our institution with CS who underwent implantation of a CRT device from 2007 to 2017. The outcomes of this population were compared with the outcomes of a cohort of patients with nonischemic cardiomyopathy with an etiology other than sarcoidosis. Nineteen patients in our institution with CS underwent CRT implantation during the time period. This group was compared with 311 consecutive patients with other etiologies of nonischemic cardiomyopathy who underwent CRT implantation. CRT improved left ventricular ejection fraction (LVEF) from 28.8% to 35.9% (p

Background Diagnostic endomyocardial biopsy (EMB) in patients with suspected myocarditis helps to direct therapy and guide prognosis. This study aimed to investigate the correlation between the 2007 clinical guideline indications for EMB and the presence of a diagnostic biopsy result and associated outcomes in patients with suspected myocarditis in a national quaternary referral center in a contemporary cohort. Methods All cases of suspected myocarditis referred to the National Cardiac Transplant Centre who underwent EMB between 2009 and 2019 were identified retrospectively through pathology records. Outcomes including subsequent need for inotrope and/or mechanical circulatory support (MCS), heart transplantation and in-hospital mortality were recorded. Results In total, 25 (68% male, mean age of 45 ± 15 years) EMBs were performed for this indication across this time period, 64% (n = 16) of which demonstrated diagnostic results, the majority (75%, n = 12) identifying acute lymphocytic myocarditis, 13% (n = 2) giant cell, one patient (6.3%) eosinophilic and one (6.3%) an immune checkpoint inhibitor myocarditis. The majority of those with histologically confirmed myocarditis had a Class I or IIa guideline indication for EMB (n = 12, 75%). The remaining 4 patients (25%), either met Class IIb criteria (n = 2) or would not have been accounted for in this guideline. The majority of patients requiring inotropes and/or MCS (n = 9/11), and/or heart transplant (n = 3/4), or who later died (n = 4/5) were in the diagnostic biopsy group. Conclusions In this 10-year National referral sample, 75% of patients with histologically confirmed myocarditis had a Class I or IIa indication for EMB, reinforcing the usefulness of traditional guidelines in this contemporary era. However, 25% of patients with a subsequent confirmed histological diagnosis had either none or a less well-established indication for EMB, highlighting the need for clinical suspicion outside of accepted clinical scenarios.

BACKGROUND: The pulmonary artery pulsatility index (PAPi) has been studied to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation, but only as a single time point before LVAD implantation. Multiple clinical factors and therapies impact RV function in pre-LVAD patients. Thus, we hypothesized that serial PAPi measurements during cardiac intensive care unit (CICU) optimization before LVAD implantation would provide incremental risk stratification for early RVF after LVAD implantation. METHODS AND RESULTS: Consecutive patients who underwent sequential pulmonary artery catherization with cardiac intensive care optimization before durable LVAD implantation were included. Serial hemodynamics were reviewed retrospectively across the optimization period. The optimal PAPi was defined by the initial PAPi + the PAPi at optimized hemodynamics. RVF was defined as need for a right ventricular assist device or prolonged inotrope use (>14 days postoperatively). Patients with early RVF had significantly lower mean optimal PAPi (3.5 vs 7.5, P < .001) compared with those who did not develop RVF. After adjusting for established risk factors of early RVF after LVAD implantation, the optimal PAPi was independently and incrementally associated with early RVF after LVAD implantation (odds ratio 0.64, 95% confidence interval 0.532−0.765, P < .0001). CONCLUSIONS: Optimal PAPi achieved during medical optimization before LVAD implantation provides independent and incremental risk stratification for early RVF, likely identifying dynamic RV reserve.

Introduction The burden of advanced heart failure (HF) is an understudied aspect of Ireland’s chronic HF population. Given an expanding menu of advanced HF therapies, identifying suitable candidates for timely assessment and intervention with progression to heart transplantation or mechanical circulatory support (MCS) if appropriate, is imperative. However, given the intensity of resource and service utilization involved, contemporaneous epidemiological and descriptive data is essential for adequate resource planning and provision. Purpose To identify demographics and outcomes of patients referred to the National Advanced HF and Cardiac Transplant centre, including identifiable markers of advanced HF according to the Heart Failure Association of the European Society of Cardiology (ESC) 2018 position statement. Methods Consecutive patients referred to the national advanced HF clinic over a 9-month period from May 2019 to February 2020 were prospectively included in this registry. Baseline demographics, laboratory, electrocardiogram, echocardiogram parameters were recorded. Markers for advanced HF according to the ESC 2018 ‘I NEED HELP’ criteria (table 1) were documented for each patient. Outcomes including need for admission from outpatient clinic, requirement for inotropes or subsequent MCS and/or heart transplantation and mortality were recorded. Results A total of 32 patients were enrolled (28% female, mean age: 49 ± 12 years, 50% NYHA III or IV) over the 9-month period. The vast majority (81%, n=25) had at least one HF hospitalization in the preceding year, with 25% (n=8) having ≥ 2. Frequency of markers of advanced HF, according to the ‘I NEED HELP’ criteria are outlined in table 1. Notably, 69% of the cohort had ≥ 3 markers of advanced HF. At the time of clinic review, 28% (n=9) required urgent admission for further assessment and management, almost all (89%, 25% of total cohort) of these requiring inotropes. Out of the total cohort, 31% subsequently underwent MCS implantation (median: 33 ± 13 days) or heart transplantation (median 38 ± 22 days) (table 2). At time of clinic visit, 37.5% had a relative contraindication to transplantation with 16% having ≥ 2, the most frequently observed being elevated body mass index (BMI) >30 kg/m2, excess alcohol intake and renal dysfunction with an estimated glomerular filtration rate Conclusion Referrals to the National Advanced HF service in Ireland are presenting at an already markedly advanced stage, with over two-thirds having 3 or more established markers of advanced HF, a quarter requiring direct admission leading to inotropes, and almost a third proceeding to advanced surgical therapies. In addition, more than one third of patients referred had a relative contraindication identified at first consultation, with lifestyle factors accounting for a significant proportion. These findings have implications for development of formal referral pathways and greatly increased resource provision to a hitherto understudied cohort to enable optimal assessment and management for this patient group.

Introduction Diagnostic endomyocardial biopsy (EMB) in patients with myocarditis helps to direct therapy and guide prognosis. The original 2007 joint scientific statement provided guideline indications based on unique clinical scenarios, detailing who should undergo this invasive investigation but have not been studied in a contemporary cohort of suspected myocarditis patients. Purpose To investigate the correlation between the clinical guideline indications for EMB and the presence of a diagnostic biopsy result and associated outcomes in patients with suspected myocarditis in a national quaternary referral center. Methods All cases of suspected myocarditis referred to the National Advanced Heart Failure and Transplant Center between 2009–2019 were identified through pathological records. A thorough retrospective chart review was then performed on all patients. Outcomes including need for inotrope or mechanical circulatory support (MCS), heart transplantation and in-hospital mortality were recorded. Results In total, 25 (68% male, mean age of 45 ± 15 years) EMBs were performed for suspected myocarditis between 2009–2019, 64% (n=16) of which demonstrated diagnostic results. Clinical characteristics of those with histologically confirmed myocarditis are represented in figure 1. Regarding pathologic subtypes, 81% (n=13) identified an acute lymphocytic myocarditis, 13% (n=2) giant cell myocarditis and one patient (6.3%) eosinophillic myocarditis. The majority of those with a histologically confirmed myocarditis had a Class I or IIa guideline indication for EMB (n=12, 75%). All patients requiring inotropes and/or MCS (n=9) and/or heart transplant (n=3) were in this group. The remaining 4 patients (25%), of whom three were diagnosed with acute lymphocytic myocarditis and one an immune checkpoint inhibitor (ICI) myocarditis, either met Class IIb criteria (n=2) or would not have been accounted for in this guideline. Four patients (25%) died during the index admission, one of whom was in the latter group (histologically confirmed myocarditis without a 2007 guideline indication). Conclusions In this National referral sample, 75% of patients with suspected myocarditis had a Class I or IIa indication for EMB, reinforcing the usefulness of these guidelines even in a contemporary era. Further, existing guideline indications appeared to identify a sicker group of patients more frequently requiring inotropes, MCS and/or heart transplant. However, in the contemporary era, 25% of patients had either none or a less well established indication for EMB despite a subsequent confirmed histological diagnosis, including a case of immune checkpoint inhibitor myocarditis, which has emerged since the publication of the 2007 guidelines. This highlights the need for clinical suspicion and correlation outside of accepted clinical scenarios.

Introduction Accurate prevalence data for advanced heart failure (HF), reported to range between 2–10% of the chronic HF population, are lacking. Determining the proportion of patients potentially suitable for referral to a specialist advanced HF center is crucial for accurate service planning and resource provision, particularly in the evolving era of durable mechanical circulatory support. Purpose To identify the population of patients potentially eligible for referral for assessment for advanced surgical therapies to the National Advanced HF and Cardiac Transplant center, using a quick one-page prospective survey. Methods A survey comprising 13 potential markers of advanced HF was developed, modified from the 2018 position statement of the Heart Failure Association of the European Society of Cardiology. This was distributed to 26 HF clinic centers nationally. Each center was asked to complete the survey on consecutive patients over a 3-month period who fulfilled the following three criteria: 1) age 3 months duration. Results In all, 21 of 26 HF clinic centers participated in the survey. Across the period of inclusion, 4950 all-comer HF patients were seen in 21 centers. Of these, 375 fulfilled the inclusion criteria, comprising 279 (74.4%) males with a median age of 57 years. In total, 246 (66%) of the completed surveys had one or more potential markers for advanced HF, representing just under 5% of the total all-comer HF population seen across the same time period. Of these, 67 patients (27%) had at least two, 48 (20%) had three and 40 (16%) had ≥ 4 potential markers. The most frequently noted markers were ≥1 hospitalization or unscheduled clinic review (56%), intolerance to renin-angiotensin-aldosterone system inhibitors due to hypotension or renal dysfunction (29%) and intolerance to beta-blockers due to hypotension (27%). Almost one-quarter of patients reported NYHA Class III or IV symptoms (figure 1). Conclusions In this index prospective National survey, approximately 5% of an all-comer routine HF clinic population and two-thirds of a pre-selected HF with reduced EF

Relief of congestion is the primary goal of initial therapy for acute decompensated heart failure (ADHF). Early measurement of urine sodium concentration (UNa) may be useful to identify patients with diminished response to diuretics. The aim of this study was to determine if the first spot UNa after diuretic initiation could select patients likely to require more intensive therapy during hospitalization.At the time of admission, 103 patients with ADHF were identified prospectively, and UNa was measured after the first dose of intravenous diuretic. Clinical outcomes were compared for patients with UNa60 mmol/L and UNa of ≤60 mmol/L, with the primary outcome of a composite of death at 90 days, mechanical circulatory support during admission, and requirement of inotropic support at discharge.Patients with UNa ≤60 had lower admission blood pressure, had less chronic neurohormonal antagonist prior to admission, and were more than twice as likely to experience the primary end point (hazard ratio 2.40, 95% CI 1.02-5.66, P = .045), which was marginally significant after adjusting for renal function and baseline home loop diuretic. Worsening renal function was significantly more common in patients with UNa60 (23.6% vs 6.5%, P = .05). Although the initial assessment of congestion was similar at admission, patients with low early UNa had a longer length of stay (11 vs 6 days, P .006) than patients with UNa60.Assessment of spot UNa after initial intravenous loop diuretic administration may facilitate identification and triage of a population of HF patients at increased risk for adverse events and prolonged hospitalization.

AIMS The utility of combined assessment of both frailty and cognitive impairment in hospitalized heart failure (HF) patients for incremental post-discharge risk stratification, using handgrip strength and Mini-Cog as feasible representative parameters, was investigated. METHODS AND RESULTS A prospective, single-centre cohort study of older adults (age ≥65) hospitalized for HF being discharged to home was performed. Pre-discharge, grip strength was assessed using a dynamometer (Jamar hydrolic hand dynamometer, Lafayette Instruments, Lafayette, IN, USA) and was defined as weak if the maximal value was below the gender-derived and body mass index-derived cut-offs according to Fried criteria. Cognition was assessed using the Mini-Cog. The presence of impairment was defined as a score of

Cardiogenic shock from biventricular failure that requires acute mechanical circulatory support carries high 30 day mortality. Acute mechanical circulatory support can serve as bridge to orthotopic heart transplant (OHT) in selected patients. We report a patient with biventricular failure secondary to rapidly progressive cardiac sarcoidosis refractory to medical management who was bridged to OHT with Impella 5.0 and Impella RP—temporary left and right ventricular assist devices, respectively. This is the first successful bridge to transplantation using these devices in biventricular heart failure and cardiogenic shock. We discuss considerations for using this strategy over veno‐arterial extracorporeal membrane oxygenation or surgically implanted assist devices in patients with cardiogenic shock and biventricular failure as a bridge to OHT.

The association between atrial fibrillation (AF) and thromboembolic (TE) complications in left ventricular assist device (LVAD) recipients is controversial, and there is paucity of large-scale data evaluating the impact of AF on early outcomes after device implantation. Using the National Inpatient Sample, we identified hospitalizations where patients underwent LVAD implantation from 2010 to 2015. Multivariate logistic regression was used to evaluate the association of AF on in-hospital outcomes. A total of 18,378 patients (41.7% with AF) underwent LVAD implantation. Patients with AF were older (59.9 vs. 54.0 years, p 0.001), more commonly male (79.9 vs. 74.1%, p 0.001), and had a greater burden of comorbidities as measured by the Elixhauser comorbidity index (7.2 vs. 6.3, p 0.001). Patients with AF had less incidence of ischemic stroke (3.1 vs. 4.7%, p = 0.04, OR 0.68), hemorrhagic stroke (1.0 vs. 2.4%, p = 0.006, OR 0.43), and other systemic embolism (1.8 vs. 3.7%, p = 0.01, OR 0.55). There was no significant difference in the incidence of bleeding requiring transfusion between AF and no AF cohorts (29.3 vs. 24.2%, p = 0.09, OR 1.15). LOS was shorter in patients with AF (32.9 vs. 36.7 mean days, p 0.001). Patients with AF had lower in-hospital mortality (8.9 vs. 14.9%, p 0.001, OR 0.48). In a large real-world US cohort of patients undergoing LVAD implantation, a diagnosis of AF was common among device recipients. After adjustment for demographics and comorbidities, AF was associated with reduced TE events and in-hospital mortality.

Background: Secondary palliative care (SPC) provides several benefits for patients with cardiovascular disease, but historically, it has been underutilized in this population. Prior research suggests a low rate of SPC consultation by surgical teams in general, but little is known about how surgical teams utilize SPC in the setting of severe cardiovascular disease. Aim: To determine if surgical team assignment affects the probability of SPC for inpatients dying of cardiovascular disease. Design: Retrospective, cohort study. Methods: We identified all inpatients at a large cardiac hospital who had anticipated death under the care of a cardiology, cardiac surgery, or vascular surgery team in 2016. Our primary outcome was referral to SPC, including palliative medicine consultation or inpatient hospice care. Informed by univariate analysis, we created a multivariable logistic regression model, the significance of which was assessed with the Wald test. Results: Two hundred thirty-seven patients were included in our analysis: 93 (39%) received SPC and 144 (61%) were “missed opportunities.” Secondary palliative care was less frequent in patients assigned to a surgical, versus medical, team (11% vs 47%, P < .001). On multivariate analysis, surgical versus medical team assignment was the strongest risk-adjusted predictor of SPC (odds ratio [OR]: 0.10, P < .001). Other predictors of SPC included do not resuscitate status on admission (OR: 14, P < .001), length of stay (OR = 1.05/day, P < .001), and having Medicare (OR = 3.9, P = .002). Conclusions: Primary inpatient care by a surgical team had a strong inverse relationship with SPC. This suggests a possible cultural barrier within surgical disciplines to SPC.

Purpose Antifungal prophylaxis in heart transplantation is not universally prescribed in our institution. We reviewed the incidence of invasive fungal diseases (IFD) in heart transplants, risk factors, and diagnostic yield of culture and nonculture-based testing for IFD. Methods A 5-year retrospective audit of heart transplant recipients in a national transplant centre from 2015 to 2019 was conducted. Proven and probable IFD were identified based on host factors, clinical features and mycological evidence outlined by the updated EORTC/MSGERC definitions. Results The incidence of proven or probable IFD was 14% (11/77) with 207 median days (IQR 54.5-306) post-transplant to diagnosis. 4 (36%) cases occurred 0.05). Of the 7 with rejection, median time from transplant to 1st rejection was 17 days (IQR11-51), and 1st rejection to IFD was 125 days (IQR 44-191). 45% (5/11) with IFD had required post-operative renal replacement therapy. 45% had neutrophils Conclusion Antifungal surgical prophylaxis could have prevented 1 IFD. A cohort of high-risk heart transplant recipients may benefit from antifungal prophylaxis.

Background It is increasingly recognized that pump thrombosis most likely represents the end stage of a complex interaction between the patient-pump interface. We hypothesized that early patient/pump mismatch, as manifested by suboptimal left ventricular (LV) unloading early after left ventricular assist device (LVAD) implantation, may be a harbinger of increased risk for later LVAD thrombosis. Methods In 64 patients (59 ± 11 years old, 78% men, 44% destination therapy) discharged alive without thrombosis or other device malfunction after first HeartMate II LVAD implantation (between January 2011 and June 2014), LV dimensions in end diastole (LVIDd) and end systole (LVIDs) were compared between pre-implant and optimal set speed pre-discharge echocardiography. LV dimension decrement indices (pre-implant dimension − optimal set speed dimension ÷ pre-implant dimension × 100) for LVIDd [LVIDdDI] and LVIDs [LVIDsDI] were calculated. Results The incidence of pump thrombosis was 0.06 per patient year ( n = 18, median time 8 [interquartile range 2, 17] months). Baseline characteristics including pre-operative LVIDd and LVIDs were similar between LVAD thrombosis and no thrombosis groups. After ventricular assist device implantation, set speed and other ramp parameters did not differ between groups. However, LVIDdDI (19 ± 13% vs 25 ± 11%, p = 0.04) and LVIDsDI (16 ± 16% vs 27 ± 13%, p = 0.008) were significantly lower in patients with later pump thrombosis. A cutoff value of ≤15% using receiver operating characteristic curve analysis was 83% sensitive for LVIDdDI and LVIDsDI for predicting pump thrombosis. Patients with LVIDdDI of >15% vs ≤15% were significantly more likely to be free of pump thrombosis over a median follow-up period of 15 (interquartile range 9, 26) months (log-rank test, p = 0.045). Conclusions LV dimension decrement index at optimized speed setting on pre-discharge echocardiography is associated with LVAD thrombosis.

Introduction Mitral regurgitation (MR) resulting from a markedly dilated left ventricle (LV) is common in advanced heart failure patients undergoing LV assist device (LVAD) implant. Significant MR post-LVAD therapy can contribute to worsening pulmonary venous hypertension, right ventricular (RV) failure, morbidity and mortality. Our aim was to examine the impact of MR severity on survival outcomes in patients on LVAD support. Methods A single-center retrospective chart review was conducted for any patient with LVAD implant for demographic, clinical, and echocardiographic variables. Post-LVAD MR severity was used to categorize patients into minimal or significant MR groups. Significant (severe) MR was defined by the presence of EROA ≥0.4cm2, regurgitant volume ≥60ml, regurgitant fraction ≥50%, jet >40% of LA, or grade ≥2+. Results 270 patients (mean age 57 ± 12 years) were analyzed. The majority were male (84%), and had non-ischemic cardiomyopathy (60%), bridge-to-transplant LVAD therapy (52%), significant pre-implant MR (75%), and minimal post-LVAD MR (87%). Median survival time after LVAD implant was 5.96 vs 4.74 years among patients with minimal vs significant MR, respectively (p=0.50). No significant difference was seen between groups even after adjusting for age, gender and device indication (hazard ratio 1.49 [95% CI 0.91, 2.24], p=0.119). Median survival time post-LVAD was 4.90 vs 5.41 years among patients with vs without grade ≥1 MR improvement post-LVAD, respectively (p=0.30). Overall, 28 patients (45%) and 75 patients (36%) died in the respective significant and minimal MR cohorts post-LVAD. Conclusions In our cohort, a minority of patients had persistence of significant MR on LVAD support. Survival outcomes on LVAD support or as bridge to heart transplant did not differ based on MR severity post-LVAD implant. Future studies are warranted on the implications of post-LVAD MR severity on hospital readmission burden.

Introduction Hereditary transthyretin amyloidosis (hATTR) is a progressive multisystem disorder with a wide clinical spectrum. In the Irish population, the T60A variant is the most common genotype. We aimed to describe the spectrum of patients with T60A hATTR attending an Irish national amyloid clinic. Methods The medical, laboratory and radiological records of all patients attending our cardiac amyloidosis referral clinic with a confirmed diagnosis of T60A variant hATTR were reviewed. Results The T60A mutation accounted for 94% of our hATTR population (15 patients; 60% male; median age at diagnosis of 65 years [IQR = 63,67], median follow up 10 months [IQR 4,60]). The majority (80%) were symptomatic at presentation with the remainder referred for family screening. Ten patients (66%) had a family history suggestive of amyloidosis; six of these had a first degree relative with a T60A mutation. Neurological manifestations predated cardiac manifestations and were present in 93% of patients at the time of diagnosis (peripheral neuropathy in 80% and autonomic neuropathy in 95%). Five patients (33%) had undergone a bilateral carpal tunnel release procedure at a median of 11 years (IQR 9, 13) pre-diagnosis. Symptoms of heart failure were present in 53% during follow up (New York Heart Association class II 40%; class III 13%; the remainder remained asymptomatic) while 33% had a heart failure hospitalisation over the past year. All patients had cardiac involvement at presentation by Technitium-99m, 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy (Perugini Grade 2 in 40%; Grade 3 in 60%). Only those with symptoms had ventricular hypertrophy on echocardiography (median left ventricular wall thickness 2cm (IQR 1.5, 2.5); median right ventricular (RV) wall thickness 0.8cm [IQR 0.68, 0.92]). Due to abnormalities on haematological testing, 9 patients (60%) required tissue confirmation of ATTR (RV endomyocardial biopsy in 5; rectal, bladder or fat pad in 3; bone marrow aspirate in 1). All patients were heterozygous for the T60A variant. All patients received disease modifying treatment at some point during follow-up (diflunisal 80%; doxycycline 7%; patisiran 33% and tafamidis 7%). All patients with Perugini grade 2 on initial Tc-DPD imaging progressed to grade 3 on repeat imaging at a median interval of 18 months (IQR 6.75, 36). Conclusions T60A variant hATTR presents with a mixed phenotype of polyneuropathy and heart failure. Neurological manifestations are more prevalent at an earlier stage while cardiac involvement by TC-DPD is already at an advanced stage at the time of diagnosis irrespective of symptoms and progressed over short term follow-up in our cohort.

Purpose To determine overall survival outcomes and outcomes according to gender and era of transplantation, for cardiac transplant recipients in the Republic of Ireland and compare these against international published registry data. Methods A retrospective registry was created of all heart transplants performed in the National Heart and Lung Transplant Centre, Dublin between 1985 and 2019. Kaplan Meier analysis and log rank comparison testing were performed for overall mortality as well as subgroup analyses. This data was then compared to international figures published annually by the ISHLT. Results Overall survival: Median survival was 13.27 years in comparison to 10.9 years internationally over a similar time period. Gender differences: 22.4% of transplants were in females. Median survival in males was 13.9 years and 12.07 years in females (p=0.028). Internationally, median survival was 10.7 years for males and 11.7 years for females. Decade transplanted: Median survival increased from 10.25 years for transplants performed in the 1980s to 15.03 years for those performed 2000-2009 (p=0.034) with survival curves suggesting improved survival for those transplanted after 2010. This compares favourably to ISHLT data: 10.5 years (1992-2001) and 12.4 years (2002-2008). One year survival: This increased from 69.5% for transplants performed in the 1980s, 78% for 1990-1999; 81% for 2000-2009 and 89% for 2010-2019. Conditional on survival to 1 year: Overall median survival was 16.07 years. This has increased from 12.9 years for transplants performed in the 1980s to 18.27 years for those performed 2000-2009 (p=0.069). Conclusion Survival rates post cardiac transplantation in the Republic of Ireland have increased significantly from the beginning of the program in 1985 and compare favourably to international registry data. Based on data since 2000, 1 year survival is now 89%; median survival is at least 15 years and conditional on surviving to 1 year, median survival is at least 18.27 years.

Purpose Identify the prevalence and associates of ISHLT grade ≥2R acute cellular rejection (≥2CR) and its impact on survival post heart transplantation in a well-phenotyped, modern era Irish cohort all of whom receive induction therapy. Methods Retrospective analysis of 88 patients who underwent heart transplantation between 2014 and 2019 (mean age 49.8 ± 13.02 years; female 29.5%). Data was collected on recipient and donor anthropometrics, HLA profile, panel reactive antibodies (PRAs) ischaemia time, cytomegalovirus (CMV) serostatus and endomyocardial biopsy results over a median follow up of 2.04 years (IQR 3.18). Kaplan Meier survival, univariate and multivariate cox regression analysis were performed. Results Standard immunosuppression was with basiliximab induction, a calcineurin inhibitor, steroid and antimetabolite. All-cause mortality at 1 year was 14%. In those patients surviving to first biopsy (n=82), 55% experienced at least 1 episode of ≥2CR at a median time of 53.5 days (IQR 149) and cumulative survival was reduced in this group (p=0.04). More than 1 episode of ≥2CR was not associated with an incremental mortality risk. Intermediate-high risk CMV serostatus was independently associated with increased mortality on multivariate analysis (HR 3.16; 95%CI 1.04-9.65; p=0.04) but not with an increased risk of ≥2CR. There was no association between ischaemic time, PRAs, other recipient/donor matching characteristics, number of HLA mismatches or mismatches confined to any of the 6 HLA subclasses on survival or development of ≥2CR. Conclusion In a modern era Irish cohort where induction therapy is standard, patients who experienced ≥1 episode of ≥2CR post transplant had reduced survival. Intermediate-high risk CMV serostatus was the only independent associate of increased mortality but not for ≥2CR. Further work in an extended cohort will focus on understanding the mechanisms underpinning rejection in this contemporary population and its consequences.

Over 30,000 ventricular assist devices (VADs) have been implanted worldwide in the past decade. Continuous-flow VAD therapy has realized greater durability and improved survival. Both axial and centrifugal flow devices are approved for the treatment of chronic and refractory advanced heart failure. Patients waiting for transplants that are ‘bridged’ and transplant-ineligible patients (destination therapy), receive VAD therapy. One-year survival rates are now approximately 80% and 70% at 2 years. The advent of continuous-flow VADs replaced volume displacement pulsatile VADs and numerous adverse events related to lack of circulatory pulsatility became recognized and prevalent as VAD therapy proliferated. Common adverse events include driveline infection, device infection, haemorrhagic and embolic stroke, bleeding, aortic insufficiency, and VAD thrombosis. Current VAD therapy requires systemic anticoagulation and antiplatelet therapy. A lack of donor hearts has resulted in prolonged and frequent VAD therapy in transplant candidates. Careful selection of VAD candidates is imperative and requires careful risk stratification. New VAD models with technological advances will enhance patient acceptance of VAD therapy and lead to further expansion in advanced heart failure patients.

Background Higher body mass index ( BMI ) is associated with lower circulating levels of N‐terminal‐pro‐b‐type natriuretic peptide ( NT ‐pro BNP ). The Interaction between BMI and NT ‐pro BNP with respect to clinical outcomes is not well characterized in patients with acute heart failure. Methods and Results A total of 686 patients from the biomarker substudy of the ASCEND ‐ HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated HF ) clinical trial with documented NT ‐pro BNP levels at baseline were included in the present analysis. Patients were classified by the World Health Organization obesity classification (nonobese: BMI 2 , Class I obesity: BMI 30–34.9 kg/m 2 , Class II obesity BMI 35–39.9 kg/m 2 , and Class III obesity BMI ≥40 kg/m 2 ). We assessed baseline characteristics and 30‐ and 180‐day outcomes by BMI class and explored the interaction between BMI and NT ‐pro BNP for these outcomes. Study participants had a median age of 67 years (55, 78) and 71% were female. NT ‐pro BNP levels were inversely correlated with BMI ( P NT ‐pro BNP levels were associated with higher 180‐day mortality (adjusted hazard ratio for each doubling of NT ‐pro BNP, 1.40; 95% confidence interval, 1.16, 1.71; P NT ‐pro BNP on 180‐day death was not modified by BMI class (interaction P =0.24). Conclusions The prognostic value of NT ‐pro BNP was not modified by BMI in this acute heart failure population. NT ‐pro BNP remains a useful prognostic indicator of long‐term mortality in acute heart failure even in the obese patient. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT00475852.

Continuous-flow left ventricular assist devices (LVAD) have become an increasingly utilized treatment strategy for patients with end-stage heart failure. Despite the improved outcomes evident with current generation pumps, proper patient selection remains crucial to minimize the risk of potential adverse events. The evolving use of these devices as destination therapy (DT) has led to growing numbers of patients with higher risk comorbid conditions being evaluated as potential LVAD candidates. Understanding which patient and disease-specific characteristics increase postoperative morbidity and mortality is paramount as this technology continues to expand and the experience with select populations remains limited. Presented here is a case of a patient with systemic lupus erythematosus receiving a HeartWare LVAD as DT complicated by recurrent, diffuse spontaneous bleeding. The case presented here highlights a potential unique bleeding complication in a high-risk patient cohort and underscores the need to enhance our understanding of factors influencing outcomes in high-risk populations after LVAD therapy.

Purpose PAPi (pulmonary artery pulsatility index) is a predictor of early right ventricular failure (RVF) post left ventricular assist device (LVAD) implantation and has been studied using hemodynamics from single, isolated time points. Since multiple clinical factors and therapies are known to impact RV function in pre-LVAD patients, we hypothesized that serial PAPi measurements would provide incremental risk stratification for early post-LVAD RVF. Methods A total of 394 consecutive patients undergoing primary durable LVAD implantation at our center from 2004 to 2017 were retrospectively enrolled. Serial invasive hemodynamics obtained during inpatient swan guided therapy (77%) or consecutive outpatient right heart catheterizations were recorded. The lowest, highest (“Best”), change (“Delta”) and most proximal PAPi to LVAD implant were calculated. RVF was defined as need for RVAD or prolonged inotrope use > 14 days post-operatively. Multivariate logistic regression determining independent associates of early RVF was performed. Results RVF occurred in 82 of the 394 patients (21%). Those who developed early RVF had significantly lower mean Delta PAPi (2.0 vs 5.3, p Conclusion The best PAPi achieved during medical optimization prior to LVAD implantation provides independent and incremental risk stratification for early RVF, likely identifying RV reserve.

Purpose Right ventricular dysfunction (RVD) and mitral regurgitation (MR) are associated with poor outcomes after left ventricular assist device (LVAD) implantation, and residual MR post-implantation may be associated with poor RV outcomes. We sought to assess predictors of change in MR in patients implanted with continuous flow (CF) LVADs. Methods 286 patients implanted with CF-LVADs between Jan 2011 - Dec 2015 were analyzed. Demographic, laboratory, clinical and hemodynamic data were obtained from electronic records. Echocardiograms within 3-months prior to and within 3-months after surgery were reviewed. A total of 35 potential predictors of change in MR severity pre and post LVAD underwent initial univariable analysis. Variables with p Results Mean age was 57 (± 12) years, 84% were male, bean LVEF was 17 (± 6.4) %, and indexed left ventricular end diastolic volume (LVEDVi) was 130 (± 61) ml/m2. For changes in MR post-op, age, LVEDVi, indexed left atrial volume, degree of pre-op MR, diabetes mellitus, CKD, INTERMACS level, cardiac output, cardiac index, RV stroke work index, sphericity index, average mitral annular diameter, tenting area and coaptation length were identified. On multivariable analysis, LVEDVi and degree of pre-op MR were significant predictors (p = 0.010 and Conclusion For changes in degree of MR, higher pre-operative LVEDVi was associated with worse MR post-surgery, and more severe pre-op MR was associated with improvement in degree of MR post-operatively. These findings suggest pre-implant echocardiographtic assessment of LV size and MR severity can identify patients at increased risk of post-LVAD significant MR. Further analysis is needed to verify the findings of this exploratory study and to determine the effect on clinical outcomes.

QRS Fragmentation and QTc in Hypertrophic CardiomyopathyBackground QRS fragmentation (fQRS) and prolonged QTc interval on surface ECG are prognostic in various cardiomyopathies other than hypertrophic cardiomyopathy (HCM). The association between fQRS and prolonged QTc duration with occurrence of ventricular tachyarrhythmias or sudden cardiac death (VTA/SCD) in patients with HCM was explored. Methods and Results One hundred and ninety-five clinical HCM patients were studied. QTc duration was derived applying Bazett's formula; fQRS was defined as presence of various RSR’ patterns, R or S notching and/or >1 additional R wave in any non-aVR lead in patients without pacing or (in)complete bundle branch block. The endpoints comprised SCD, ECG documented sustained VTA (tachycardia or fibrillation) or appropriate implantable cardioverter defibrillator (ICD) therapies (antitachycardia pacing [ATP] or shock) for VTA in ICD recipients (n = 58 [30%]). QT prolonging drugs recipients were excluded. After a median follow-up of 5.7 years (IQR 2.7–9.1), 26 (13%) patients experienced VTA or SCD. Patients with fQRS in ≥3 territories (inferior, lateral, septal, and/or anterior) (p = 0.004) or QTc ≥460 ms (p = 0.009) had worse cumulative survival free of VTA/SCD than patients with fQRS in

Aims The utility of combined assessment of both frailty and cognitive impairment in hospitalized heart failure (HF) patients for incremental post‐discharge risk stratification, using handgrip strength and Mini‐Cog as feasible representative parameters, was investigated. Methods and results A prospective, single‐centre cohort study of older adults (age ≥65) hospitalized for HF being discharged to home was performed. Pre‐discharge, grip strength was assessed using a dynamometer (Jamar hydrolic hand dynamometer, Lafayette Instruments, Lafayette, IN, USA) and was defined as weak if the maximal value was below the gender‐derived and body mass index‐derived cut‐offs according to Fried criteria. Cognition was assessed using the Mini‐Cog. The presence of impairment was defined as a score of

Background— Better survival for overweight and obese patients after ST-segment–elevation myocardial infarction (STEMI) has been demonstrated. The association between body mass index (BMI), outcome, and left ventricular (LV) structure and function after STEMI, including LV longitudinal strain (global longitudinal strain), was evaluated. Methods and Results— First patients with STEMI undergoing primary percutaneous coronary intervention (n=1604; mean age, 61±12 years; 75% men) had BMI measured on admission, and 2-dimensional transthoracic echocardiography performed within 48 hours. Patients were categorized based on standard criteria (normal/underweight, BMI2 [n=486]; overweight, 25≤BMI2 [n=820]; obese, BMI≥30 kg/m 2 [n=298]). LV global longitudinal strain was measured using speckle-tracking analysis. Primary outcome measure was all-cause mortality. Compared with normal/underweight patients, obese patients were younger and more likely to have diabetes mellitus, hypertension, and hyperlipidemia and have higher discharge blood pressures. Despite no significant differences in infarct size, obese patients had significantly more impaired LV global longitudinal strain (−13.7±3.8 versus −15.0±4.2% and −15.0±4.1%; P P =0.04) after STEMI during a median follow-up of 5.2 (3.6, 6.9) years on Kaplan–Meier analysis, a significant nonlinear association between BMI and all-cause mortality across the range of BMI was seen, persisting after adjustment for age and sex. Conclusions— Obese patients demonstrate greater adverse LV remodeling and more impaired LV deformation after STEMI compared with those with normal BMI, amid similar infarct characteristics. Normal weight patients continue to demonstrate the worst survival, suggesting that the potential nonadverse effect of higher BMI in this population is independent of LV function.

Aims To explore the association of changes in weight and fluid during treatment for acute heart failure (AHF) with clinical endpoints. Methods and Results Weight and net fluid changes recorded at 72–96 hours in 708 AHF patients enrolled in Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure, Cardiorenal Rescue Study in Acute Decompensated Heart Failure, and Renal Optimization Strategies Evaluation in Acute Heart Failure studies were compared with freedom from congestion at 72–96 hours and a composite endpoint of death, rehospitalization, and unplanned hospital visit at 60 days. Weight loss was concordant with net fluid loss in 55%, discordant and less than expected for fluid loss in 34%, and paradoxically discordant or more than expected for fluid loss in 11% of patients. Weight loss, but not fluid loss, was associated with freedom from congestion (odds ratio per 1-kg weight loss = 1.11 [1.03–1.19]) and a nominal reduction in the composite endpoint (hazard ratio per 1-kg weight loss = 0.98 [0.95–1.00]). Outcomes were similar in patients with concordant and discordant weight-fluid loss. Conclusion During treatment for AHF, early changes in weight may be more useful for identifying response to therapy and for predicting outcomes than net fluid output. Nearly one-half of patients receiving decongestive therapies demonstrate discordant changes in weight and fluid; however, discordance was not associated with outcomes.